With an increasing risk of nuclear and radiological emergencies, there is a critical need for development of medical radiation countermeasures (MRC) which are safe, easily administered and effective in preventing and/or mitigating the potentially lethal tissue damage caused by radiation exposure, especially high-dose radiation exposure (e.g. ARS). There are currently no FDA approved MRCs. Commercially available granulocyte colony-stimulating factor (G-CSF, filgrastim) has been of interest as a MRC; however, G-CSF has only shown variably positive results in animal studies, has limited utility in mass-casualty situations due to the need for multiple injections, supportive care, and laboratory monitoring, and is not approved by FDA for this purpose. The inflammatory cytokine interleukin (IL)-12 has also been evaluated, but did not demonstrate consistently significant radiomitigation in animal studies, has substantial inflammatory toxicity in humans, has not undergone a defined animal-to-human dose-conversion plan, and is unapproved by FDA for any use.
CBLB502 is a truncated derivative of the Salmonella flagellin protein that acts by triggering Toll-like receptor 5 (TLR5) signaling and has shown great promise in development as a MRC. The efficacy of MRCs, including CBLB502, for preventing and/or mitigating the potentially lethal tissue damage caused by radiation exposure is difficult to assess since they cannot be ethically tested in humans. There remains a need for safe and effective doses of MRCs, like CBLB502.